A diverse set of malignant and oncogenically transformed mammalian cells in culture will not grow when the amino acid methionine is replaced by its immediate metabolic precursor homocysteine. Normal cells on the other hand divide rapidly under these conditions. We have previously found that the malignant and oncogenically transformed cells synthesize methionine from homocysteine and thus their inability to grow in homocysteine-containing medium is not due to lack of methionine. The inability of the cancer cells to grow in homocysteine-containing medium may be due to elevated levels of S-adenosylhomocysteine, a potentially toxic metabolite of homocysteine. We propose to further investigate the biochemical basis of this defect, to further understand the relationship of the defect to the cancerous state and to attempt to utilize the knowledge gained for the treatment of cancer.